rs11166965

chr8-140252916-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001160372.4(TRAPPC9):c.2292C>T(p.Gly764=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,613,104 control chromosomes in the GnomAD database, including 13,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1091 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12531 hom.)
• Consequence: TRAPPC9 NM_001160372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.33

Genes affected

TRAPPC9 (HGNC:30832): (trafficking protein particle complex subunit 9) This gene encodes a protein that likely plays a role in NF-kappa-B signaling. Mutations in this gene have been associated with autosomal-recessive cognitive disability. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 8-140252916-G-A is Benign according to our data. Variant chr8-140252916-G-A is described in ClinVar as [Benign]. Clinvar id is 130625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC9	NM_001160372.4	c.2292C>T	p.Gly764=	synonymous_variant	16/23	ENST00000438773.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.2292C>T	p.Gly764=	synonymous_variant	16/23	1	NM_001160372.4	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16065 AN: 152044 Hom.: 1084 Cov.: 32

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0999

GnomAD3 exomes AF: 0.128 AC: 31915 AN: 249722 Hom.: 2606 AF XY: 0.123 AC XY: 16656 AN XY: 135234

Gnomad AFR exome AF: 0.0342

Gnomad AMR exome AF: 0.244

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.00224

Gnomad SAS exome AF: 0.0764

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.124 AC: 181349 AN: 1460942 Hom.: 12531 Cov.: 32 AF XY: 0.123 AC XY: 89092 AN XY: 726766

Gnomad4 AFR exome AF: 0.0284

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.00164

Gnomad4 SAS exome AF: 0.0775

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.106 AC: 16083 AN: 152162 Hom.: 1091 Cov.: 32 AF XY: 0.108 AC XY: 8004 AN XY: 74384

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0697

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.0984

Alfa AF: 0.122 Hom.: 1658

Bravo AF: 0.102

Asia WGS AF: 0.0590 AC: 207 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.120

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Intellectual Disability, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.085
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11166965; hg19: chr8-141263015;